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2013 Joint Conference of Drug Safety Research Centres

In affiliation with the Pacific Rim Association for Clinical Pharmacogenetics (PRACP)

Thomas Y.K. Chan

Division of Clinical Pharmacology

Department of Medicine and Therapeutics, and

Centre for Food and Drug Safety, Faculty of Medicine

The Chinese University of Hong Kong, and

Prince of Wales Hospital Poison Treatment Centre

16 October 2013

Preventing and Managing

Drug Induced Anaphylactic Shock

Using Pharmacogenomics to Improve Drug Safety and Efficacy

Preventing/managing drug induced anaphylaxis

Depend on a good understanding of the pathophysiology

of anaphylaxis, subjects at risk, drugs involved, usual and

usual presentation, prospects for prevention, management

approach and reasons for continuing morbidity/mortality

• Case reports – avoidable, unusual, fulminant

• Causes and intrinsic/extrinsic risk factors for anaphylaxis

• Mechanisms, clinical features and grading of anaphylaxis

• Management approach – adrenaline as the first-line drug

• Strategies – prevention, recognition and management

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Drug-induced anaphylaxis should be avoidable

M/55, allergic rhinitis, asthma, known allergy to aspirin

and ibuprofen for ~8 years

Took diclofenac 100 mg (own stock) for left knee pain

Sudden onset of SOB, wheeze and flushing 3 h later

Arrived in ED 40 min after onset of symptoms

BP 142/86 mmHg, pulse 104 bpm, RR 32 breaths/min

SaO2 95% (O2 4 L/min), diffuse rhonchi

Adrenaline (1:1000) 0.5 ml i.m.

Hydrocortisone 200 mg i.v., chlorpheniramine 10 mg i.v.

Salbutamol and ipratropium MDI

Home after staying in EMW for 12 hours

Drug-induced anaphylaxis could have been missed

F/55, found collapsed in shopping mall, GCS 3, pupils 3

mm, ambulance arrived in 10 min, spontaneous breathing but

cyanosed, bagging (SaO2 3085%)

Intubated in A&E, BP 179/98 mmHg, pulse 119 bpm, SaO2

99%, 4 limb movements, rhonchi, salbutamol/ipratropium

Woke up 1.5 h and extubated 2 h after ICU admission, acute

onset of SOB before LOC 1 h after taking levofloxacin 1 tab

for toothache, vomited once

Stayed in ICU for 25.5 h and in ward for 2 days

cardiac troponin 79.5 ng/L (<14), ALT 100 IU/L (<55),

WBC 12.3 x 109/L (<9.7), ECG normal

On discharge, BP 118/70 mmHg

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Drug-induced anaphylaxis could be rapidly fatal

M/51, IVU as out-patient, iopamidol (water-soluble non-

ionic, monomeric, iodinated radiocontrast medium)

After the injection, vomiting, LOC and pulseless, CPR

started, pulseless electrical activity on ECG

Adrenaline 1 mg i.v., fluids i.v. orientated, SBP ~140

mmHg, chest pain, ST ↓ on ECG, faecal incontinence,

very red appearance (vasodilation)

Cardiac arrest, LOC, CPR started, adrenaline 1 mg iv,

narrow complex rhythm, asystole or VF on ECG, DC

shock given, failed resuscitation

Autopsy epiglottis swelling, pulmonary congestion,

coronary atherosclerosis and cardiomegaly

What is anaphylaxis

An acute, potentially life-threatening hypersensitivity reaction,

involving the release of mediators (e.g. histamine) from tissue

mast cells, circulating basophils, recruited inflammatory cells

Multisystem signs and symptoms occurring within minutes or

up to a few hours, after exposure to provoking agents – severe

allergic reactions with CVS and/or RS features

Can be mild, moderate to severe or severe

Developing rapidly, usually reaching peak severity within 5-30

minutes, and may, rarely, last for several days

3-23% of episodes followed by biphasic reactions hours later

(Adapted from: Lockey RF 2004 and Confino-Cohen R et al. 2010)

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What is anaphylactic shock

Anaphylaxis accompanied by hypotension (SBP >30% ↓ from

baseline or <90 mmHg in adults)

Rarely, patients present with isolated acute hypotension

The main cardiovascular changes during anaphylaxis = fluid

extravasation and vasodilation (causing a mixed distributive–

hypovolaemic shock) plus ↓ myocardial contractivity

Blood volume may decrease by up to 35% within 10 minutes

due to extravasation; severe vasodilation may only respond to

potent vasoconstrictors

Risk factors for shock in anaphylaxis – old age, anti-HT drugs

(Brown SGA. Immunol Allergy Clin N Am 2007; 27: 165-75)

(Lee S et al. J Allergy Clin Immunol 2013; 131: 1103-8)

Causes of anaphylaxis – Hong Kong

Common causes differ between children (foods) and adults (drugs)

282 patients (166M, 116F) aged 1-91 years (median 28) with

anaphylaxis, Prince of Wales Hospital ED, 3/1999 to 2/2003

A precipitant identified in 89%, with 19% of patients claiming

a known allergy to the precipitant

Foods = 49.6% of cases (seafoods – 71%)

Drugs = 40.5% of cases (NSAIDs/aspirin – 25.5%, antibiotics

– 23.5%, Chinese medicines – 21.6%)

Insect bites/stings = 7.1%

Plants/hair dye = 1.6%, gas inhalation = 0.4%, idiopathic = 0.8%

(Smit DV et al. J Emerg Med 2005; 28: 381-8)

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Drugs causing anaphylaxis – Europe

National Pharmacovigilance System, Portugal

1/2000-10/2010, 918 anaphylaxis cases (6% of ADR reports)

Age 7 days-91 years, mean 48 years, 9% ≤18 years

F = 70% of adults, M = 56% of paediatric population

Antibiotics (17%), NSAIDs/paracetamol (13%), cytotoxic

drugs (12%), immune-modulators (9%), vaccines (7%) and

radiocontrast media (4 %)

19% led to hospitalisation, 24 (3%) had a fatal outcome

Anaphylaxis can occur at any age and is mostly caused by

widely used drugs (e.g. antibiotics and analgesics)

(Ribeiro-Vaz I et al. Eur J Clin Pharmacol 2013; 69: 673-81)

Intrinsic risk factors for anaphylaxis

• Previous history of anaphylaxis – however, at least

25% of adults and 65% of children with anaphylaxis

do not report a previous episode

• Atopy – orally administered drugs, radiocontrast media,

latex, exercise, idiopathic anaphylaxis

• Female gender – aspirin, muscle relaxants, diagnostic

agents, idiopathic anaphylaxis

• Increased socio-economic status

• ↓ vitamin D level (sunlight exposure) – a strong north-

south gradient in the US for EpiPens prescriptions

(Lee JK et al. Clin Exp Allergy 2011; 41: 932-8; Ben-Shoshan M et al. Allergy 2011; 66: 1-14)

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Group Name of gene Comments

Anatomic barrier genes Filaggrin Increased risk of developing allergic sensitisation and not necessarily anaphylaxis

Innate immunity genes NLRP3: SNPs (rs4612666 and rs10754558) Significantly associated with susceptibility to food-induced anaphylaxis

Innate immunity and

mast cells genes

C-KIT Mutations associated with anaphylaxis after hymenoptera stings and may also

underlie cases of idiopathic anaphylaxis

SWAP-70 Anaphylactic responses are strongly reduced in mice with mutations in this gene

PAF V279F (>30% of Japanese subjects) Mutations increase the risk for various inflammatory diseases in Japanese subjects

PAF and PAF-AH activity affect severity of anaphylaxis

Sphk1 Sphingosine 1-phosphate receptors play a critical role in regulating human mast cell

functions, including degranulation and cytokine and chemokine release

Rcan Rcan1 is a novel negative regulator in FcεRI-induced mast cell activation

CCRL2 Enhance tissue swelling and leucocyte infiltrates

Adaptive immunity STAT-6 (13/15-GT repeat heterozygosity

and the 15GT repeat homozygosity)

Polymorphisms higher in children in Japanese population with allergic disease

IL-4 (Ile75Val variant of IL-4R∝ gene) Polymorphisms of IL-4 have been implicated in drug allergy especially in women

IL-10 (-819 C>T and -592 C>A variants) Polymorphisms of IL-10 promoter associated with β-lactam anaphylactic reactions

IL-13, 18 (promoter polymorphisms in

IL13-1055, IL18-607 and IL18-656)

Latex allergy phenotype significantly associated with polymorphism in the promoter

site of these cytokines

Unknown function DOCK8 Absence of DOCK8 protein associated with severe atopy and anaphylaxis

Genes implicated in the pathogenesis of anaphylaxis

Adapted from: Ben-Shoshan M al el. Allergy 2011; 66: 1-14

Mechanisms of anaphylaxis Most cases are IgE mediated, but it is not possible to distinguish IgE from non-IgE cases

Anaphylaxis

Allergic (immunologic)

anaphylaxis

Non-allergic (non-

immunologic) anaphylaxis

IgE mediated Non-IgE mediated (IgG mediated, complements and

coagulation system activation,

immune complexes, etc.)

Direct activation

of mast cells

Excessive amounts of IgE are produced during sensitisation. Specific IgE binds to high affinity IgE receptors

(FcεRI) on mast cells and basophils. Re-exposure to allergen leads to cross-linking of receptor-bound IgE,

triggering cell activation and release of mediators.

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Preformed for immediate release

Histamine Vasodilation and oedema, bronchoconstriction, mucus secretion, nerve stimulation, ↓ myocardial contractility (H1 receptor), ↑

myocardial contractility (H2 receptor)

Heparin Anticoagulant, anti-inflammatory, mediates capillary leakage and oedema formation by initiating the formation of bradykinin

(a vasoactive and proinflammatory peptide hormone)

Tryptase Amplification of allergic response (+ve feedback on effector cells), leucocyte migration and activation, bronchoconstriction,

vasodilation and oedema, tissue degradation and cell proliferation

Chymase Vasodilation and oedema, mucus secretion, leucocyte activation, tissue degradation

Tumour necrosis factor (TNF-α) Bronchoconstriction, leucocyte adhesion, leucocyte migration and activation, possible role in delayed-phase reactions

Newly generated over minutes

Cyclooxygenase products, mainly PGD2 Vasodilation and oedema, bronchoconstriction, mucus secretion, nerve stimulation (vasodilation, itching, bronchoconstriction)

Lipoxygenase products: LTB4, LTC4, LTD4, LTE4 Vasodilation and oedema, mucus secretion, bronchoconstriction, leucocyte recruitment

Platelet-activating factor (PAF) Platelet activation/microthrombi, leukocyte migration/activation, histamine release (indirectly by neurogenic activation), ↓

myocardial contractility

Newly generated over hours

IL-5, GM-CSF Leucocyte adhesion, leucocyte migration and activation

IL-4, IL-13 IgE production and upregulation of FcεRI expression

IL-10 Anti-inflammatory, ↓ activation and degranulation of mast cells, induces ↑ numbers of Tregs

IL-6 Proinflammatory cytokine; correlates with the extent of erythema and inversely related to MAP; correlates strongly with

occurrence of hypotension; causes ↑ expression of FcεRI, ↑ intracellular histamine, and prevents mast cell apoptosis

sTNFRI Surrogate marker for TNF-α activity, may have anti-inflammatory effects

PAF-AH Enzyme that inactivates PAF, low levels reported in fatal anaphylaxis

Anaphylatoxins (C3a, C4a, C5a) Complement activation products, mast cell and neutrophil degranulation and smooth muscle contraction

Chemokines (ie, RANTES, IL-8, MCP-1) Chemotaxis and activation of immune cells, histamine and serotonin release from mast cells

Mediators of anaphylaxis Known/possible effects – the lungs and the heart are the major shock organs

Adapted from: Stone SF al el. Curr Allergy Asthma Rep 2012; 12: 33-41

Patient-specific risk factors for anaphylaxis severity and fatality

Age Comorbidities Concurrent medications /

recreational drugs

• Infant: cannot describe

symptoms and difficult to

diagnose anaphylaxis

• Adolescent / young adult:

↑ risk of anaphylaxis

triggered by foods

- Inconsistent behaviour

regarding allergen

avoidance and carrying

adrenaline autoinjector

• Elderly: greater risk of

fatality from insect

venom anaphylaxis and

concomitant diseases

(e.g. COPD, CVD)

• Asthma especially if

severe or uncontrolled

• CVD

• Allergic rhinitis and

eczema: atopic

diseases are a risk

factor for anaphylaxis

triggered by foods,

exercise and latex

• Psychiatric disease

(may impair

recognition of

symptoms)

• May affect recognition

of anaphylaxis:

sedatives, hypnotics,

antidepressants, alcohol

narcotics, recreational

drugs

• May increase the

severity of anaphylaxis:

𝛽 blockers, ACE

inhibitors

• May affect responses to

adrenaline: 𝛽 blockers

Adapted from: Stoloff SW. J Fam Pract 2010; 59: S1-8

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Multiple logistic regression analysis adjusted ORs (95% CI) in 302 ED adult cases for the association between antihypertensive

drugs and markers of severe anaphylaxis (syncope, hypoxia or hypotension) (A); 3 or more organ system involvement (B); and

hospitalisation adjusted for gender, age, suspected trigger and preexisting lung disease (C).

Lee S et al. J Allergy Clin Immunol 2013; 131: 1103-8

Simons FE et al. Curr Opin Allergy Clin Immunol 2012; 12: 389-99

Clinical criteria for diagnosis of anaphylaxis (with CVS and/or RS features)

In infants and children, respiratory compromise is more likely than hypotension or shock, and shock is more likely to be manifest initially

by tachycardia than by hypotension.

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History of asthma 54 (19.1%)

History of allergy 116 (41.1%)

Clinical features

・Urticaria 223 (79.1%)

・Angioedema 171 (60.6%)

・Flushing or general pruritus 209 (74.1%)

・Dyspnoea 185 (65.6%)

・Wheeze/bronchospasm 85 (30.1%)

・Laryngeal oedema 31 (11%)

・Tongue swelling 21 (7.5%)

・Chest pain – non-specific 16 (5.7%)

・Angina 1 (0.35%)

・Abdominal pain or diarrhoea 27 (9.6%)

・Vomiting 23 (8.2%)

・Dysphagia 1 (0.35%)

・Headache 2 (0.71%)

・Syncope 16 (5.7%)

・Dizziness 39 (13.8%)

・Systolic BP (mmHg) 129 [108.5-150]

・Diastolic BP (mmHg) 68 [55.5-81]

・Peak expiratory flow rate (L/min) 300 [220-400]

282 patients with anaphylaxis, Prince of Wales Hospital, 3/1999 to 2/2003

Smit DV al el. J Emerg Med 2005; 28: 381-8

Numbers (%) of patients or medians (IQR [25–75])

Severity Defined by

Mild

(skin and subcutaneous tissues

only)†

Generalised erythema, urticaria,

periorbital oedema or angioedema

Moderate

(features suggesting respiratory,

cardiovascular or

gastrointestinal involvement)

Dyspnoea, stridor, wheeze, nausea,

vomiting, dizziness (presyncope),

diaphoresis, chest or throat

tightness or abdominal pain

Severe

(hypoxia, hypotension or

neurological compromise)

Cyanosis or SpO2 ≤92%,

hypotension (SBP <90 mmHg in

adults), confusion, collapse, loss of

consciousness or incontinence

Severity of generalised hypersensitivity reactions

Adapted from: Brown SGA. Emerg Med Australas 2006; 18: 155-69

†The Mild grade does not represent anaphylaxis according to the National Institute of Allergy and Infectious Disease-Food

Allergy and Anaphylaxis Network and World Allergy Organization definitions.

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294 Korean subjects admitted to the ED with anaphylaxis, 1/2000-12/2009

Park HJ et al. Am J Emerg Med 2012; 30: 1674-8

Symptoms or signs, n (%) Non-shock (n=175) Shock (n=119) P value

Cutaneous

Urticaria

Itching

Flushing

Angioedema

166 (94.9)

99 (56.6)

69 (39.4)

41 (23.4)

28 (16.0)

97 (81.5)

50 (42.0)

61 (51.3)

32 (26.9)

15 (12.6)

<.001

.014

.045

.500

.419

Respiratory

Dyspnoea

Hoarseness

Cyanosis

Laryngeal oedema

Cough

Wheezing

100 (57.1)

93 (53.1)

6 (3.4)

2 (1.1)

5 (2.9)

5 (2.9)

5 (2.9)

68 (57.1)

65 (54.6)

2 (1.7)

21 (17.6)

1 (0.8)

1 (0.8)

5 (4.2)

1.000

.803

.480

<.001

.407

.407

.533

Cardiovascular

Syncope

Chest discomfort

Palpitation

Sweating

Cardiac arrest

50 (28.6)

3 (1.7)

40 (22.9)

3 (1.7)

4 (2.3)

0 (0.0)

102 (85.7)

45 (37.8)

16 (13.4)

3 (2.5)

15 (12.6)

1 (0.8)

<.000

<.001

.044

.689

<.001

.405

Gastrointestinal

Nausea

Vomiting

Abdominal pain

Diarrhoea

56 (32.0)

22 (12.6)

19 (10.9)

25 (14.3)

19 (10.9)

34 (28.6)

21 (17.6)

21 (17.6)

10 (8.4)

4 (3.4)

.531

.227

.096

.126

.019

Neurologic

Dizziness

Headache

Seizure

27 (15.4)

23 (13.1)

6 (3.4)

0 (0.0)

61 (51.3)

59 (49.6)

3 (2.5)

2 (1.7)

<.001

<.001

.743

.163

Characteristics Non-biphasic (n=195) Biphasic (n=13) P value

Male (%) 106 (54.4) 4 (30.8) 0.173

Median age, years 22 18.5 0.564

Atopy (%) 118 (60.5) 4 (30.8) 0.069

- Allergic rhinitis (%) 47 (22.6) 4 (30.8) 0.526

- Asthma (%) 31 (15.9) 3 (23.1) 0.771

- Food allergy (%) 45 (23.1) 2 (15.4) 0.764

Drug allergy (%) 36 (18.5) 0 0.13

Previous allergic reactions (%) 78 (40) 5 (38.5) 0.855

Underlying disease (%) 87 (44.6) 5 (38.5) 0.885

Presenting symptoms:

・Urticaria/angioedema (%) 169 (86.7) 12 (92.3) 1.00

・Bronchospasm (%) 100 (51.3) 4 (30.8) 0.252

・Abdominal pain (%) 57 (29.2) 7 (53.8) 0.121

・Hypotension (%) 63 (32.3) 5 (38.5) 0.879

・Shock (%) 56 (28.7) 5 (38.5) 0.665

・Unconsciousness (%) 7 (3.6) 1 (7.7) 0.409

Treatment:

・Intramuscular injection of adrenaline (%) 170 (87.2) 13 (100) 0.467

・Adrenaline use (%) 192 (98.5) 12 (92.3) 0.229

・Injected H1 antagonist (%) 180 (92.30 11 (84.6) 0.288

・Injected H2 antagonist (%) 114 (58.5) 9 (69.2) 0.636

・Steroid use (%) 169 (86.7) 10 (76.9) 0.398

・β-agonist use via nebuliser (%) 59 (30.3) 4 (30.8) 1.00

Time interval Median (IQR) Median (IQR)

・Time from contact – onset (minutes) 30 (17.5-107.5) 120 (10-240) 0.501

・Time from onset – hospital arrival (minutes) 60 (30-120) 180 (105-360) 0.002

・Time from onset – adrenaline (minutes) 70 (40-135) 240 (122.5-380) 0.002

・Time from hospital arrival – adrenaline (minutes) 15 (10-15) 25 (16.5-30) 0.001

208 cases of anaphylaxis with or without biphasic reactions, Thailand, 2004-2008

Lertnawapan R al el. Allergol Int 2011; 60 :283-9

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Soar J et al. Resuscitation 2008; 77: 157-69.

Pros

• Adrenaline has a vasodilation effect in skeletal muscle

• Skeletal muscle is highly vascular, leading to rapid absorption

• Drug injected into vastus lateralis reaches central circulation

promptly

• Peak pharmacologic effects are achieved promptly

• Benefit-to-risk ratio perceived to be optimal when this route is used

for first-aid treatment

• Most commonly recommended route worldwide Cons

• Currently available auto-injector needle lengths and gauges are not

optimal for intramuscular injection in overweight or obese people

• Not effective if muscle perfusion is poor or absent due to shock or

cardiorespiratory arrest

Adrenaline – pros / cons of intramuscular administration in anaphylaxis

Simons KJ et al. Curr Opin Allergy Clin Immunol 2010; 10: 354-61

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Pros

• Optimal route of administration for patients with severe anaphylaxis who have

not responded to intramuscular adrenaline and/or are experiencing profound

hypotension or shock, or in whom cardiorespiratory arrest is imminent

Cons

• Establishing a peripheral intravenous route for adrenaline administration may

be difficult in the above patients

• Narrower benefit-to-risk ratio than adrenaline administered by other routes,

partly attributed to iatrogenic error

• For safe administration in hypotension or shock, it is optimally given through

an infusion pump and central line by physicians trained and experienced in

continuous dose titration of vasopressors against continuously monitored heart

rate and function, blood pressure and oxygenation

• Errors in adrenaline dosing combined with errors in assessment of cardiac rate

and function and blood pressure can be catastrophic for the patient

Adrenaline – pros / cons of intravenous administration in anaphylaxis

Simons KJ et al. Curr Opin Allergy Clin Immunol 2010; 10: 354-61

ED management

・IV fluids 88 (31.2%)

・Adrenaline (i.v., i.m., s.c.) 188 (66.7%)

・H1 antagonists 269 (95.4%)

・H2 antagonists 4 (1.4%)

・Steroids 258 (91.5%)

・Salbutamol 95 (33.7%)

・Ipratroprium 44 (15.6%)

・Intubation 4 (1.4%)

Disposition

・Discharge ED 4 (1.4%)

・Discharge against advice 9 (3.2%)

・Observation ward 154 (54.6%)

・General ward 93 (33%)

・Intensive care unit 27 (7.8%)

282 patients with anaphylaxis, Prince of Wales Hospital, 3/1999 to 2/2003

Smit DV et al. J Emerg Med 2005; 28: 381-8

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Follow-up care of patients with anaphylaxis

Patients should understand their drug allergy status and

action plans in case of emergency

Further work up and referral to the experts

Skin prick testing is useful to help identify the cause of

anaphylaxis, but does not predict the severity of reactions

Except for β-lactam antibiotics and a few other drugs,

such allergens are generally not available for skin testing

or in vitro testing

The level of serum specific IgE does not correlate with

reaction severity and cannot be used to identify subjects

at risk for anaphylaxis

(Lee JK et al. 2011 and Simons FER 2009)

Waserman S et al. Allergy 2010; 65: 1082-92

Theme Description Gap

Anaphylaxis

management

Lack of knowledge to identify the signs and

symptoms, or correctly diagnose anaphylaxis

Adrenaline is not the most commonly prescribed

treatment

Patients are not diagnosed accurately

Lack of awareness and adequate knowledge of anaphylaxis

No published criteria or professional consensus on prescribing adrenaline for

severe allergy

Infrequent, inappropriate or no use of adrenaline

Auto-injector prescription is low

Adrenaline use

Inadequate or no training provided to patients

on how to use adrenaline auto-injectors

Adrenaline administration is inadequate or delayed

Physicians lack knowledge on epinephrine use

Parents of children with allergies have unmet information needs from

their physicians, including not knowing the definition of anaphylaxis and

the symptoms requiring epinephrine

Patients receive infrequent or no instruction, demonstration, or training

on how to use auto-injectors

Patients unsure when or how to use an auto-injector

Adrenaline either not given or administration was delayed

Lack of knowledge or consensus on appropriate dosage of adrenaline

Few physicians have or know how to use an auto-injector training device

In acute severe reactions, differences exist on treatment recommendations, and

adrenaline is used less than other medications (e.g. steroids, β blockers)

Follow-up care

Infrequent or no referral to an allergy

specialist after acute reaction

Patients are not given enough information

about how to manage anaphylaxis

Patients do not have an anaphylaxis action plan

Few patients are being referred to an allergy specialist after an allergic reaction

Lack of follow-up is common in patients who experienced an acute reaction

Physicians did not think that advising patients to go to the hospital after

taking adrenaline was necessary

Few patients are given accurate information and advice by their family

physicians about managing anaphylaxis

Few patients with acute allergic reactions were given discharge instructions

Poor identification of or provision of guidance of which allergens to avoid

Patients do not have action plans or there is no consensus on what should be included

in action plans; missing essential components or auto-injector instructions

Anaphylaxis management gaps categorised by a Canadian panel of allergy experts in a systematic review

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Anaphylaxis – Prevention, Recognition, Management

Anaphylaxis can occur at any age and is mostly caused by widely

used drugs (e.g. antibiotics, analgesics, cytotoxic drugs, RCM)

Drug induced anaphylaxis is preventable by checking and clearly

documenting drug allergy status and educating patients

Drug induced anaphylaxis can have unusual clinical presentations,

biphasic reactions, rapid clinical deterioration and fatal outcome

Patient-specific risk factors for anaphylaxis severity and fatality –

age, comorbidities (CVD, COPD) or concomitant drugs

Markers of severe anaphylaxis – including very rapid onset, shock,

cyanosis, syncope, neurological compromise

Adrenaline i.m. and fluids i.v. – first-line treatment of anaphylaxis

Continuing training to address gaps in knowledge and management